The general notion of an “RNA World” is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA and genetically encoded proteins were not involved as catalysts. There is now strong evidence indicating that an RNA World did indeed exist before DNA- and protein-based life.However, arguments regarding whether life on Earth began with RNA are more tenuous. It might be imaginedthat all of the components of RNA were available in some prebiotic pool, and that these components assembled into replicating, evolving polynucleotides without the prior existence of any evolved macromolecules. A thorough consideration of this “RNA-first” view of the origin of life must reconcile concerns regarding the intractable mixtures that are obtained in experiments designed to simulate the chemistry of the primitive Earth. Perhaps these concerns will eventually be resolved, and recent experimental findings provide some reason for optimism. However, the problem of the origin of the RNA World is far from being solved, and it is fruitful to consider the alternative possibility that RNA was preceded by some other replicating, evolving molecule, just as DNA and proteins were preceded by RNA.

Bat flight poses intriguing questions about how flight independently developed in mammals. Flight is among the most energy-consuming activities. Thus, we deduced that changes in energy metabolism must be a primary factor in the origin of flight in bats. The respiratory chain of the mitochondrial produces 95% of the adenosine triphosphate (ATP) needed for locomotion. Because the respiratory chain has a dual genetic foundation, with genes encoded by both the mitochondrial and nuclear genomes, we examined both genomes to gain insights into the evolution of flight within mammals. Evidence for positive selection was detected in 23.08% of the mitochondrial-encoded and 4.90% of nuclear-encoded oxidative phosphorylation (OXPHOS) genes, but in only 2.25% of the nuclear-encoded nonrespiratory genes that function in mitochondria or 1.005% of other nuclear genes in bats. To address the caveat that the two available bat genomes are of only draft quality, we resequenced 77 OXPHOS genes from four species of bats. The analysis of the resequenced gene data are in agreement with our conclusion that a significantly higher proportion of genes involved in energy metabolism, compared with background genes, show evidence of adaptive evolution specific on the common ancestral bat lineage. Both mitochondrial and nuclear-encoded OXPHOS genes display evidence of adaptive evolution along the common ancestral branch of bats, supporting our hypothesis that genes involved in energy metabolism were targets of natural selection and allowed adaptation to the huge change in energy demand that were required during the origin of flight.

Author contributions: Y.-Y.S. and Y.-P.Z. designed research; Y.-Y.S. and L.L. performed research; Y.-Y.S., Z.-H.Z., W.-P.Z., and Y.-P.Z. analyzed data; and Y.-Y.S., D.M.I., and Y.-P.Z. wrote the paper.

The authors declare no conflict of interest.

Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. GQ427677–GQ427913 andGU292797-GU292809).

Source/Fonte Not related to this article/Não relacionado com este artigo

Summary

The presence of inactive units in tandem arrays of ribosomal genes (rDNA) has been linked to increased transcriptional capacity, but a recent study indicates that inactive units are necessary for sister chromatid cohesion and genetic stability of rDNA.

segunda-feira, abril 26, 2010

Published Sunday, April 25, 2010 in Opinion
'This is not intelligent design'

Darwinian evolutionists now belong to the category of phrenologists and flat-earthers. You don't have to be a creationist to realize that gradual evolution simply could not have occurred as Darwin proposed.

Swedish scientist Loren [sic. Soren] Lovetrup (not a creationist) says: "I believe that one day the Darwinian myth will be ranked the greatest deceit in the history of science," adding that "evolution is anti-science" and "false."

Biochemist Michael Behe has shown in his book, "Darwin's Black Box," that complex systems exist which simply could not have evolved gradually. He calls this "irreducible complexity" -- that is, every part must be in place at the same time for it to work.

domingo, abril 25, 2010

Mathematicians Offer Elegant Solution to Evolutionary Conundrum

ScienceDaily (Apr. 25, 2010) — UBC researchers have proffered a new mathematical model that seeks to unravel a key evolutionary riddle--namely what factors underlie the generation of biological diversity both within and between species.

Evolutionary biologists have long recognized that the emergence of rare traits within a population can spur diversity. For example, being one of a few under-sized predators in a population dominated by larger-sized predators can offer advantages--access to an abundance of small prey--and increase the likelihood of that trait prospering in the population.

"But existing mathematical models that incorporate these 'rare type' advantages tend to have some serious shortcomings," says Michael Doebeli, a researcher at UBC's Biodiversity Research Centre and professor with the departments of Mathematics and Zoology."They rely on single traits--like body size--and predict that the advantage offered by that trait has to be very significant in order to maintain large amounts of diversity."

The mechanisms for the origin and maintenance of biological diversity are not fully understood. It is known that frequency-dependent selection, generating advantages for rare types, can maintain genetic variation and lead to speciation, but in models with simple phenotypes (that is, low-dimensional phenotype spaces), frequency dependence needs to be strong to generate diversity. However, we show that if the ecological properties of an organism are determined by multiple traits with complex interactions, the conditions needed for frequency-dependent selection to generate diversity are relaxed to the point where they are easily satisfied in high-dimensional phenotype spaces. Mathematically, this phenomenon is reflected in properties of eigenvalues of quadratic forms. Because all living organisms have at least hundreds of phenotypes, this casts the potential importance of frequency dependence for the origin and maintenance of diversity in a new light.

Department of Zoology and Department of Mathematics, University of British Columbia, 6270 University Boulevard, Vancouver, BC V6T 1Z4, Canada.

It is doubtful if any single book, except the 'Principia', ever worked so great and so rapid a revolution in science, or made so deep an impression on the general mind [as On the Origin of Species]. 1
T.H. Huxley

… the name of Charles Darwin stands alongside of [that] of Isaac Newton … and, like [it], calls up the grand ideal of a searcher after truth and interpreter of Nature . . . [The present generation] thinkls] of him who bore it as a rare combination of genius, industry, and unswerving veracity, who earned his place among the most famous men of the age by sheer native power.!
T.H. Huxley

All educated persons are familiar with the notion that life on this planet has arisen through a process of evolution. Most people have been taught that the proper name of this theory is ‘Darwinism’, the reasons being that Charles Darwin was the first person to state the idea about organic evolution and furthermore originated the theory of natural selection, which unambiguously accounts for the mechanism through which the process of evolution is realised.

The concept of ‘evolution’ unites all branches of biology, and a person who accomplished these two feats would indeed be greatest among biologists, and might well deserve the epithet: ‘The Newton of Biology’. As appears from the above quotations, Huxley did not hesitate to bestow this honour upon his friend Charles Darwin.

In fact, this comparison was no invention of Huxley’s; ironically enough it appears that Alfred Wallace was the first to come upon this idea, for on 1 September 1860 he wrote to his friend George Silk: ‘Darwin’s “Origin of Species” … you may have heard of and perhaps read, but it is not one perusal which will enable any man
to appreciate it. I have read it through five or six times, each time with increasing admiration. It will live as long as the “Principia” of Newton. ,3

As might almost have been predicted, it was also heralded by Ernst Haeckel. Some few years after the publication of On the Origin of Species, quoting Immanuel Kant, he wrote:

‘ … it is absurd for man even to conceive such an idea, or to hope that a Newton may one day arise able to make the production of a blade of grass comprehensible, according to natural laws ordained by no intention; such an insight we must absolutely deny to man’. Now, however, this impossible Newton has really appeared seventy years later in Darwin, whose Theory of Selection has actually solved the problem, the solution of which Kant has considered absolutely inconceivable!”

Thus, Huxley was not the first, and still less the last one prepared to elevate Darwin to the pinnacles of glory in the history of biology; even today this opinion is shared almost unanimously by all who feel entitled to judge in these matters.

It is important to observe, however, that Huxley makes the comparison between Newton and Darwin with regard to two separate points: the impact of their work and their intellectual excellence.

Surely, no sensible person would contend Huxley’s first assertion; it is indeed true that no other book ever had the influence on the state of science commanded by On the Origin of Species. Is it a corollary that its author was a towering genius, foremost among biologists?

It may not be easy to give a direct answer to this question, and I shall therefore approach the problem by dealing with the two claims made above on behalf of Darwin. Thus (1) is Darwin the founder of the theory of evolution and (2) does his theory of natural selection give an acceptable explanation of the mechanism of evolution? If these two points are indeed borne out, then Darwin may well be the ‘Newton of Biology’ – otherwise not.

In this book I propose to show that in both instances the answer is ‘no’; and if I am right, we obviously end up in a rather awkward situation as far as present-day biology is concerned. But before we reach this point it would be well to outline the issue.

The main tenet of Darwin’s theory is that his natural selection accomplishes evolutionary changes through the accumulation of some of those very slight individual variations which occur in all populations of living beings. The selection of these variations, and hence the direction of evolution, is such that the organisms become
better adapted to the environment in which they happen to live.

Since the struggle for existence is bound to be toughest between adults, it follows that Darwin’s theory is a micromutation theory which accounts for evolutionary innovation primarily through the modification of adult organisms.

This theory was professed ex cathedra when I went to school, and for many years I accepted it without contemplation or dissent. Now and then I read literature dealing with evolution, but being an embryologist I did not think that evolution was of direct concern to me. I do not know when I first began to suspect that there is something questionable in the state of current evolutionary thought, but I know who aroused my suspicions – Karl Ernst von Baer’ and Richard B. Goldschmidt,” and it is because I am an embryologist that their teachings had this effect. These two zoologists quite clearly demonstrated that the origin of the major animal taxa must be sought in modifications of the epigenetic, and notably the morphogenetic processes through which the fertilised egg is transformed, first into an embryo or a larva, and subsequently to a slightly deformed miniature of the adult organism. (This last statement is not valid for animals that undergo extensive metamorphosis.) And the main inference from this insight is that many of the mutations which have been really important from an evolutionary point of view must have been one-stroke changes of features distinguishing disparate major taxa. In other words, the views of von Baer and Goldschmidt imply that macromutations have been of great significance in organic evolution.

I did not examine the consequences of this insight until I was engaged in writing Epigenetics – A Treatise on Theoretical Biology.’ This work aimed at elucidating some of the epigenetic mechanisms responsible for animal ontogenesis. Only at that time did I see that phylogenesis, i.e. evolution, is of primary concern for
epigenetics because phylogenetic innovations imply ontogenetic innovations. Hence I realised that my book would not be complete without a discussion of evolution, particularly a discussion of the consequences of the macromutation theory for our conception of the course and mechanism of evolution.

I therefore undertook a study of the literature on evolution, and made several discoveries which strengthened my conviction that the micromutation theory does not stand up to critical testing. Above all, I discovered that the so-called ‘Neo-Darwinism’ is fundamentally different from Darwin’s theory.

Since that time I have written several publications on evolution, adding steadily to the evidence falsifying the micromutation theory.

However, the most interesting discoveries were made when I began to delve into the history of evolutionary thought. First, I came to see what I should have realised at the outset, namely, that it is Lamarck, and not Darwin, who is the founder of the theory of evolution.

Second, I found that the macromutation theory is older than Darwinism, if not than the micromutation theory, and that it has had supporters, in varying numbers, for about one-and-a-half centuries.

Third, I came to understand that in the last century, hardly anybody, not even Darwin himself, believed that natural selection can accomplish all the events necessary for the occurrence of organic
‘evolution.

Fourth, I discovered that the history of evolutionary thought, as it is told today, contains a large number of mistakes and misrepresentations – to express it fairly mildly – all of them aimed at adulating Darwin and debunking his opponents.

Today it is still commonly claimed that Darwin’s natural selection is the evolutionary mechanism par excellence. However, this assertion is not based on any factual evidence, for nobody has ever demonstrated that natural selection can bring about anything but events that are trivial from an evolutionary perspective. And this brings me to the fifth point. Since the publication of On the Origin of Species, and particularly since the Second World War, a lot of empirical observations have been made which may be used to test the evolutionary theories. And the remarkable result is that, just as Darwin found one hundred years ago, the facts obstinately corroborate the macromutation theory and falsify the micromutation theory.

These are the main discoveries I have made in the course of my studies, and I propose to present them in detail on the following pages.

The championship of a heretical point of view is a delicate matter which requires better corroboration than might otherwise be called for. For this reason I have decided to let the dramatis personae speak their own cases as far as possible, and therefore a large part of the following text consists of quotations. This fact does not, of course, guarantee impartiality; against accusations of inequity I can only say that I have done my best. One circumstance which may serve to support this claim is that some persons, above all the principal actor,
Charles Darwin, are quoted to present divergent, even contradictory views.

Before we deal with Darwin’s contribution, we shall first discuss a set of four theories, which in my view are required to account for organic evolution, and some aspects of the history of evolutionary’ thought before Darwin. Subsequently we shall deal with Darwin’s theory, its reception and its fate during the following century. After that follows the presentation of an alternative theory of evolution, which stands up to the problems which have remained unsolved by Darwinism. At this stage, when, in my opinion, the Darwinian myth has been refuted, it may be appropriate to scrutinize it and try to understand why it arose in the first place.

As published in The International Herald Tribune, The Washington Post and The Wall Street Journal on April 16, 2010 and in The New York Times on April 18, 2010:

It was inevitable: Jerusalem once again is at the center of political debates and international storms. New and old tensions surface at a disturbing pace. Seventeen times destroyed and seventeen times rebuilt, it is still in the middle of diplomatic confrontations that could lead to armed conflict. Neither Athens nor Rome has aroused that many passions.

For me, the Jew that I am, Jerusalem is above politics. It is mentioned more than six hundred times in Scripture—and not a single time in the Koran. Its presence in Jewish history is overwhelming. There is no more moving prayer in Jewish history than the one expressing our yearning to return to Jerusalem. To many theologians, it IS Jewish history, to many poets, a source of inspiration. It belongs to the Jewish people and is much more than a city, it is what binds one Jew to another in a way that remains hard to explain. When a Jew visits Jerusalem for the first time, it is not the first time; it is a homecoming. The first song I heard was my mother’s lullaby about and forJerusalem. Its sadness and its joy are part of our collective memory.

Since King David took Jerusalem as his capital, Jews have dwelled inside its walls with only two interruptions; when Roman invaders forbade them access to the city and again, when under Jordanian occupation, Jews, regardless of nationality, were refused entry into the old Jewish quarter to meditate and pray at the Wall, the last vestige of Solomon’s temple. It is important to remember: had Jordan not joined Egypt and Syriain the war against Israel, the old city of Jerusalem would still be Arab. Clearly, while Jews were ready to die for Jerusalem they would not kill for Jerusalem.

Today, for the first time in history, Jews, Christians and Muslims all may freely worship at their shrines. And, contrary to certain media reports, Jews, Christians and Muslims ARE allowed to build their homes anywhere in the city. The anguish over Jerusalem is not about real estate but about memory.

What is the solution? Pressure will not produce a solution. Is there a solution? There must be, there will be. Why tackle the most complex and sensitive problem prematurely? Why not first take steps which will allow the Israeli and Palestinian communities to find ways to live together in an atmosphere of security. Why not leave the most difficult, the most sensitive issue, for such a time?

Jerusalem must remain the world’s Jewish spiritual capital, not a symbol of anguish and bitterness, but a symbol of trust and hope. As the Hasidic master Rebbe Nahman of Bratslav said, “Everything in this world has a heart; the heart itself has its own heart.”

Elie Wiesel was born in 1928 in Sighet, Transylvania, which is now part of Romania. He was fifteen years old when he and his family were deported by the Nazis to Auschwitz. His mother and younger sister perished, his two older sisters survived. Elie and his father were later transported to Buchenwald, where his father died shortly before the camp was liberated in April 1945.

After the war, Elie Wiesel studied in Paris and later became a journalist. During an interview with the distinguished French writer, Francois Mauriac, he was persuaded to write about his experiences in the death camps. The result was his internationally acclaimed memoir, La Nuit or Night, which has since been translated into more than thirty languages.

In 1978, President Jimmy Carter appointed Elie Wiesel as Chairman of the President's Commission on the Holocaust. In 1980, he became the Founding Chairman of the United States Holocaust Memorial Council. He is also the Founding President of the Paris-based Universal Academy of Cultures and the Chairman of The Elie Wiesel Foundation for Humanity, an organization he and his wife created to fight indifference, intolerance and injustice. Elie Wiesel has received more than 100 honorary degrees from institutions of higher learning.

A devoted supporter of Israel, Elie Wiesel has also defended the cause of Soviet Jews, Nicaragua's Miskito Indians, Argentina's Desaparecidos, Cambodian refugees, the Kurds, victims of famine and genocide in Africa, of apartheid in South Africa, and victims of war in the former Yugoslavia. For more than ten years, Elie and his wife Marion have been especially devoted to the cause of Ethiopian-born Israeli youth through the Foundation's Beit Tzipora Centers for Study and Enrichment.

Teaching has always been central to Elie Wiesel's work. Since 1976, he has been the Andrew W. Mellon Professor in the Humanities at Boston University, where he also holds the title of University Professor. He is a member of the Faculty in the Department of Religion as well as the Department of Philosophy. Previously, he served as Distinguished Professor of Judaic Studies at the City University of New York (1972-76) and the first Henry Luce Visiting Scholar in Humanities and Social Thought at Yale University (1982-83).

Elie Wiesel is the author of more than forty books of fiction and non-fiction, including A Beggar in Jerusalem (Prix Médicis winner), The Testament (Prix Livre Inter winner), The Fifth Son (winner of the Grand Prize in Literature from the City of Paris), and two volumes of his memoirs.

For his literary and human rights activities, he has received numerous awards including the Presidential Medal of Freedom, the U.S. Congressional Gold Medal and the Medal of Liberty Award, and the rank of Grand-Croix in the French Legion of Honor. In 1986, Elie Wiesel won the Nobel Prize for Peace, and soon after, Marion and Elie Wiesel established The Elie Wiesel Foundation for Humanity.

An American citizen since 1963, Elie Wiesel lives with his wife in Connecticut.

sábado, abril 24, 2010

Edited* by Eviatar Nevo, Institute of Evolution, Haifa, Israel, and approved March 3, 2010 (received for review September 16, 2009)

Abstract

A hypothesis is nested within a more general hypothesis when it is a special case of the more general hypothesis. Composite hypotheses consist of more than one component, and in many cases different composite hypotheses can share some but not all of these components and hence are overlapping. In statistics, coherent measures of fit of nested and overlapping composite hypotheses are technically those measures that are consistent with the constraints of formal logic. For example, the probability of the nested special case must be less than or equal to the probability of the general model within which the special case is nested. Any statistic that assigns greater probability to the special case is said to be incoherent. An example of incoherence is shown in human evolution, for which the approximate Bayesian computation (ABC) method assigned a probability to a model of human evolution that was a thousand-fold larger than a more general model within which the first model was fully nested. Possible causes of this incoherence are identified, and corrections and restrictions are suggested to make ABC and similar methods coherent. Another coalescent-based method, nested clade phylogeographic analysis, is coherent and also allows the testing of individual components of composite hypotheses, another attribute lacking in ABC and other coalescent-simulation approaches. Incoherence is a highly undesirable property because it means that the inference is mathematically incorrect and formally illogical, and the published incoherent inferences on human evolution that favor the out-of-Africa replacement hypothesis have no statistical or logical validity.

1 Department of Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America

Abstract

Determining the evolutionary relationships between fossil hominid groups such as Neanderthals and modern humans has been a question of enduring interest in human evolutionary genetics. Here we present a new method for addressing whether archaic human groups contributed to the modern gene pool (called ancient admixture), using the patterns of variation in contemporary human populations. Our method improves on previous work by explicitly accounting for recent population history before performing the analyses. Using sequence data from the Environmental Genome Project, we find strong evidence for ancient admixture in both a European and a West African population (p ≈ 10−7), with contributions to the modern gene pool of at least 5%. While Neanderthals form an obvious archaic source population candidate in Europe, there is not yet a clear source population candidate in West Africa.

Synopsis

Determining the evolutionary relationships between modern humans and fossil hominine groups such as Neanderthals has been a question of enduring interest in human evolutionary genetics. In this paper, Plagnol and Wall present a new method for addressing whether archaic human groups contributed to the modern gene pool. Using sequence data from the Environmental Genome Project, they find strong evidence for ancient admixture in both a European and a West African population, with contributions to the modern gene pool of at least 5%. While Neanderthals form an obvious archaic source population candidate in Europe, there is not yet a clear source population candidate in West Africa. The authors' results have direct implications for the competing models of modern human origins.In particular, their estimates of non-negligible contributions of archaic populations to the modern gene pool are inconsistent with strict forms of the Recent African Origin model, which posits that modern humans evolved in a single location in Africa and from there spread and replaced all other existing hominines.

Estimating the historical and demographic parameters that characterize modern human populations is a fundamental part of reconstructing the recent history of our species. In addition, the development of a model of human evolution that can best explain neutral genetic diversity is required to identify confidently regions of the human genome that have been targeted by natural selection.

Methodology/Principal Findings

We have resequenced 20 independent noncoding autosomal regions dispersed throughout the genome in 213 individuals from different continental populations, corresponding to a total of ~6 Mb of diploid resequencing data. We used these data to explore and co-estimate an extensive range of historical and demographic parameters with a statistical framework that combines the evaluation of multiple models of human evolution via a best-fit approach, followed by an Approximate Bayesian Computation (ABC) analysis. From a methodological standpoint, evaluating the accuracy of the parameter co-estimation allowed us to identify the most accurate set of statistics to be used for the estimation of each of the different historical and demographic parameters characterizing recent human evolution.

Conclusions/Significance

Our results support a model in which modern humans left Africa through a single major dispersal event occurring ~60,000 years ago, corresponding to a drastic reduction of ~5 times the effective population size of the ancestral African population of ~13,800 individuals. Subsequently, the ancestors of modern Europeans and East Asians diverged much later, ~22,500 years ago, from the population of ancestral migrants. This late diversification of Eurasians after the African exodus points to the occurrence of a long maturation phase in which the ancestral Eurasian population was not yet diversified.

Funding: Financial support was provided by Institut Pasteur, by the Centre National de la Recherche Scientifique (CNRS), and by the Agence Nationale de la Recherche (ANR) research grant (ANR-05-JCJC-0124-01) to L.Q.-M. L.B.B. was supported by a ‘Fundação para a Ciência e a Tecnologia’ fellowship (SFRH/BD/18580/2004), and E.P. by the “Fondation pour la Recherche Médicale” (FRM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

The establishment of the genetic code remains elusive nearly five decades after the code was elucidated.The stereochemical hypothesis postulates that the code developed from interactions between nucleotides and amino acids, yet supporting evidence in a biological context is lacking. We show here that anticodons are selectively enriched near their respective amino acids in the ribosome, and that such enrichment is significantly correlated with the canonical code over random codes. Ribosomal anticodon-amino acid enrichment further reveals that specific codons were reassigned during code evolution, and that the code evolved through a two-stage transition from ancient amino acids without anticodon interaction to newer additions with anticodon interaction. The ribosome thus serves as a molecular fossil, preserving biological evidence that anticodon-amino acid interactions shaped the evolution of the genetic code.

ScienceDaily (Apr. 21, 2010) — Ever since tiny bits of genetic material known as microRNA were first characterized in the early 1990s, scientists have been discovering just how important they are to regulating the activity of genes within cells.

A new study now shows that microRNAs don't just control the activity of genes within a given cell -- they also can move from one cell to another to send signals that influence gene expression on a broader scale.

Researchers at the Duke Institute for Genome Sciences & Policy (IGSP), in collaboration with groups at the Universities of Helsinki and Uppsala and the Boyce Thompson Institute for Plant Research at Cornell University, made the discovery while working out the intricate details of plant root development in Arabidopsis, a highly-studied mustard plant. Although they still don't know exactly how the microRNAs travel, it appears that this mobility allows them to play an important developmental role in sharpening the boundaries that define one plant tissue from another.

"To our knowledge, this is the first solid evidence that microRNAs can move from one cell to another," said Philip Benfey, director of the Duke IGSP Center for Systems Biology.

ScienceDaily (Apr. 21, 2010) — A new study shows that when it comes to networks of protein fibers, individual fibers play a substantial role in effectively strengthening an entire network of fibers. The research, published by Cell Press in the April 20th issue of the Biophysical Journal, describes a mechanism that explains how individual fibrin fibers subjected to significant strain can respond by stiffening to resist stretch and helping to equitably distribute the strain load across the network.

Fibrin is a fibrous protein that assembles into a remarkably strong mesh-like network and forms the structural framework of a blood clot. Failure of a clot can have fatal consequences. For example, if a portion of the clot breaks away and is carried downstream by the flowing blood, it can cause a stroke or heart attack. Although previous research has characterized the mechanical properties and behavior of fibrin networks on a macroscopic level, much less is known about the behavior of individual fibrin fibers and the distribution of strain from one fiber to the next.

"We know that network strength is determined in part by the maximum strain individual fibers can withstand, so it is of particular interest to determine how the high strain and failure characteristics of single fibrin fibers affect the overall strength of the network," says senior study author Dr. Michael R. Falvo from the Department of Physics and Astronomy at the University of North Carolina at Chapel Hill. "Further, determining how strain is shared among the constituent fiber segments in a network under imposed stress is crucial to understanding failure modes of networks and their strength."

† Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

‡ Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

§ Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

¶ Curriculum in Applied Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Received 9 September 2009;
accepted 8 December 2009.
Editor: Denis Wirtz..
Available online 18 April 2010.

Abstract

As the structural backbone of blood clots, fibrin networks carry out the mechanical task of stemming blood flow at sites of vascular injury. These networks exhibit a rich set of remarkable mechanical properties, but a detailed picture relating the microscopic mechanics of the individual fibers to the overall network properties has not been fully developed.In particular, how the high strain and failure characteristics of single fibers affect the overall strength of the network is not known. Using a combined fluorescence/atomic force microscope nanomanipulation system, we stretched 2-D fibrin networks to the point of failure, while recording the strain of individual fibers. Our results were compared to a pair of model networks: one composed of linearly responding elements and a second of nonlinear, strain-stiffening elements. We find that strain-stiffening of the individual fibers is necessary to explain the pattern of strain propagation throughout the network that we observe in our experiments.Fiber strain-stiffening acts to distribute strain more equitably within the network, reduce strain maxima, and increase network strength. Along with its physiological implications, a detailed understanding of this strengthening mechanism may lead to new design strategies for engineered polymeric materials.